Parkinson's disease (PD) is a neurodegenerative disorder characterized by slowness, stiffness and often tremor. Over 1 million Americans have PD and globally 9 million people are projected to have PD by the year 2030. To date, there is no accepted objective biological measure, i.e, biomarker, that is reflective of disease pathogenesis or of pharmacological responses to treatment. Absence of a reliable biomarker severely limits early diagnosis, research on neuroprotective therapies and appreciation of disease pathogenesis. Current radiotracing imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) lack the ability to ascertain dopamine neuronal counts as well as density. [unreadable] Likewise, magnetic resonance imaging (MRI) in its present state is not useful as a biomarker for PD. [unreadable] Therefore, there remains a need for a PD neuroimaging technique that provides a means to measure neuronal viability and density as well as address other issues of which present imaging techniques are unable to do. A method which could ascertain neuronal status as well as possible pathogenic factors such as iron would be potentially useful. Recently we developed novel MRI techniques for human studies that can be extremely helpful in providing new insights into the molecular processes characterizing neurological diseases, in particular PD. These methods utilize the so called "adiabatic" pulses (based on the sweep of the radiofrequency (RF) during the pulses) and exploit a novel MRI contrast based on the rotating frame longitudinal and transverse relaxations, T???and T???respectively, during the adiabatic pulses. T2? is sensitive to diffusion of water protons in environments with different local magnetic susceptibilities and likely reflects iron content; whileT1? reflects predominantly water-protein interactions, and, therefore might provide an indication of neuronal loss that could be used to assess PD nigral degeneration. We have demonstrated that T???- weighted pulse sequences provide a method to directly assess non-heme iron loads in the human brain at 4.7 Tesla. The strong correlation between the obtained relaxation rate constant values and the regional non-heme iron concentrations suggests utility for the T???pulse sequences in quantifying in vivo brain iron at high magnetic fields. However, T?? MRI technique still needs proper validation in order to be established as quantitative method for neuronal count. In this study we aim to determine the validity of T?? measurements to adequately reflect neuronal density in the brain. Therefore, the specificity and sensitivity of T???measurements to neuronal density are subjected here to further investigation. We will investigate functional relationship between relaxation time constants T???and T???and thus potentially the association between neuronal density and non-heme iron. PUBLIC HEALTH RELEVANCE In this project we aim to establish novel high-resolution magnetic resonance imaging (MRI) techniques, T???as quantitative method sensitive to neuronal loss and T???as method sensitive to iron loading in the brain. We will investigate the predictive/discriminatory ability of the T???using a unilateral 6-hydroxydopamine (6-OHDA) PD mouse model (intrastriatal injection of 2 ?g 6-OHDA/?L). We will study the functional relationship between T???with neuronal density and T???with iron loading in aphakia mice (where the deficit of dopaminergic neurons in substantia nigra and the pathways for survival of neurons are well investigated). Once validated, the T???technique can be used as a valuable tool to investigate if and how neuronal loss in substantia nigra is correlated with the progression of Parkinson's disease. We will investigate functional relationship between relaxation time constants T????and T???and thus potentially the association between neuronal density and nonheme iron. [unreadable] [unreadable] [unreadable] [unreadable]